AEG35156 and Docetaxel in Treating Patients With Locally Advanced, Metastatic, or Recurrent Solid Tumors

NCT00372736 | Completed Phase 1 DMC

• 3 other identifiers: I166BCAN-NCIC-IND166BCDR0000486837
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 3

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. AEG35156 may help docetaxel work better by making tumor cells more sensitive to the drug. PURPOSE: This phase I trial is studying the side effects and best dose of AEG35156 when given together with docetaxel in treating patients with locally advanced, metastatic, or recurrent solid tumors.

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Keywords

unspecified adult solid tumor, protocol specific

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose of AEG35156 in combination with docetaxel

  Doses of AEG35156 escalated as shown in protocol section 4.3 in patient cohorts given a fixed dose of docetaxel. MTD defined as that dose level at which ≥ 2/6 patients experienced DLT (as defined in protocol section 4.6)

  2-3 years

• Recommended phase II dose

  RPTD for AEG35156 defined as one dose lower than MTD

  2-3 years

Secondary Outcomes (5)

• Toxicities

  Every 3 weeks

• Pharmacokinetic profile

  Each cycle

• Antitumor activity

  Every 6 weeks

• Pharmacodynamic effects of AEG35156 on X-linked inhibitor of apoptosis levels and apoptosis in peripheral blood mononuclear cells and tumor tissue

  Each cycle

• M30/M65 cytokeratin 18 level

  Each cycle

Interventions

AEG35156 DRUG

After a recommended phase II dose (RPTD) of AEG35156 has been determined with docetaxel 75 mg/m2, patients will be accrued to the RPTD-1 plus docetaxel 100 mg/m2, and possibly RPTD plus docetaxel 100 mg/m2, to determine the RPTD of AEG35156 in combination with docetaxel 100 mg/m2 given every three weeks.

docetaxel DRUG

After a recommended phase II dose (RPTD) of AEG35156 has been determined with docetaxel 75 mg/m2, patients will be accrued to the RPTD-1 plus docetaxel 100 mg/m2, and possibly RPTD plus docetaxel 100 mg/m2, to determine the RPTD of AEG35156 in combination with docetaxel 100 mg/m2 given every three weeks.

protein expression analysis GENETIC

Cycle 1: Pre-dose on Days -2, 1, 8 and 15; repeat every 2-4 days if LFTs \> 5 x ULN1 Cycle 2: Prior to each infusion; repeat every 2-4 days if LFTs \> 5 x ULN1

reverse transcriptase-polymerase chain reaction GENETIC

Data will be summarized by descriptive statistics relevant to each of the proposed pharmacodynamic studies.

flow cytometry OTHER

Data will be summarized by descriptive statistics relevant to each of the proposed pharmacodynamic studies.

immunoenzyme technique OTHER

Data will be summarized by descriptive statistics relevant to each of the proposed pharmacodynamic studies.

immunohistochemistry staining method OTHER

The plasma concentration/ time data will be analysed using non-compartmental methods. The pharmacokinetic parameters to be determined for AEG35156 include the maximum observed plasma concentration (Cmax), the half-life (T1/2), and mean residence time (MRT).

laboratory biomarker analysis OTHER

The plasma concentration/ time data will be analysed using non-compartmental methods. The pharmacokinetic parameters to be determined for AEG35156 include the maximum observed plasma concentration (Cmax), the half-life (T1/2), and mean residence time (MRT).

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

DISEASE CHARACTERISTICS: * Histologically confirmed solid tumor * Locally advanced, metastatic, or recurrent disease that is refractory to standard curative therapy or for which no curative therapy exists * Clinically and/or radiologically documented disease * Treatment with single-agent docetaxel is a reasonable treatment option * No newly diagnosed CNS metastases * Previously treated and stable (≥ 6 months) intracranial disease allowed PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Life expectancy ≥ 12 weeks * Absolute granulocyte count ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * PT or INR and PTT normal * Creatinine normal * Bilirubin normal * AST and ALT ≤ 1.5 times upper limit of normal (ULN) * Gamma-glutamyl transferase ≤ 3 times ULN * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * No underlying serious illness or medical condition that might be aggravated by treatment or might interfere with study treatment, including, but not limited to, the following: * Serious uncontrolled infection * Significant cardiac dysfunction * Significant neurological disorder that would impair the ability to obtain informed consent * No known bleeding disorders * No prior serious allergic reaction to taxane (paclitaxel or docetaxel) * No pre-existing peripheral neuropathy ≥ grade 2 PRIOR CONCURRENT THERAPY: * More than 4 weeks since prior chemotherapy and recovered * At least 2 weeks since prior hormonal therapy or immunotherapy * At least 4 weeks since prior external-beam radiotherapy to \< 30% of marrow-bearing areas * Low-dose, nonmyelosuppressive radiotherapy allowed * At least 2 weeks since prior surgery and recovered * More than 4 weeks since prior investigational agents or new anticancer therapy * No prior nephrectomy * No other concurrent chemotherapy * No concurrent radiotherapy * Small-volume, non-myelosuppressive palliative radiotherapy allowed * No other concurrent experimental drugs or anticancer therapy * No concurrent therapeutic dose anticoagulant therapy * Non-therapeutic dose anticoagulant therapy (i.e., 1 mg daily oral warfarin) allowed

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• NCIC Clinical Trials Group: lead

Study Sites (3)

BCCA - Vancouver Cancer Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Univ. Health Network-Princess Margaret Hospital

Toronto, Ontario, M5G 2M9, Canada

Location

McGill University - Dept. Oncology

Montreal, Quebec, H2W 1S6, Canada

Location

MeSH Terms

Interventions

AEG 35156; Docetaxel; Reverse Transcriptase Polymerase Chain Reaction; Flow Cytometry; Immunoenzyme Techniques; Immunohistochemistry

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Polymerase Chain Reaction; Nucleic Acid Amplification Techniques; Genetic Techniques; Investigative Techniques; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Cytophotometry; Fluorometry; Luminescent Measurements; Photometry; Chemistry Techniques, Analytical; Immunoassay; Immunologic Techniques; Molecular Probe Techniques; Histocytochemistry; Histological Techniques

Study Officials

• Gerald Batist, MD

  McGill Cancer Centre at McGill University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 6, 2006
• First Posted: September 7, 2006
• Study Start: July 27, 2006
• Primary Completion: March 24, 2009
• Study Completion: January 6, 2012
• Last Updated: August 4, 2023

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3)